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Information on EC 5.3.1.9 - glucose-6-phosphate isomerase and Organism(s) Homo sapiens and UniProt Accession P06744

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IUBMB Comments
The enzyme from yeast catalyses the reversible conversion specifically between the alpha-D-glucose 6-phosphate and beta-D-fructofuranose 6-phosphate. The enzyme also catalyses the anomerization of both D-hexose 6-phosphates .
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Homo sapiens
UNIPROT: P06744
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
phosphoglucose isomerase, glucose-6-phosphate isomerase, glucose phosphate isomerase, autocrine motility factor, phosphoglucoisomerase, phosphohexose isomerase, neuroleukin, pgi/amf, amf/pgi, glucose 6-phosphate isomerase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Phosphoglucose isomerase
-
6-Phosphoglucose isomerase
-
-
-
-
autocrine motility factor
-
-
D-Glucose-6-phosphate isomerase
-
-
-
-
D-glucose-6-phosphate ketol-isomerase
-
-
-
-
Glucose 6-phosphate isomerase
-
-
-
-
Glucose phosphate isomerase
-
-
-
-
Glucose phosphoisomerase
-
-
-
-
Glucosephosphate isomerase 2
-
-
-
-
GPI
-
-
-
-
Hexose 6-phosphate isomerase
-
-
-
-
Hexose isomerase
-
-
-
-
Hexose monophosphate isomerase
-
-
-
-
Hexose phosphate isomerase
-
-
-
-
Hexosephosphate isomerase
-
-
-
-
Isomerase, glucose phosphate
-
-
-
-
Neuroleukin
-
-
-
-
NLK
-
-
-
-
Oxoisomerase
-
-
-
-
PGI/AMF
-
-
PGI2
-
-
-
-
PGI3
-
-
-
-
PHI
-
-
-
-
Phosphoglucoisomerase
-
-
-
-
Phosphoglucose isomerase
phosphoglucose isomerase/autocrine motility factor
-
-
Phosphohexoisomerase
-
-
-
-
Phosphohexomutase
-
-
-
-
Phosphohexose isomerase
-
-
-
-
Phosphosaccharomutase
-
-
-
-
SA-36
-
-
-
-
Sperm antigen-36
-
-
-
-
VEG54
-
-
-
-
Vegetative protein 54
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
isomerization
-
isomerization
-
-
-
-
intramolecular oxidoreduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
alpha-D-glucose-6-phosphate aldose-ketose-isomerase (configuration-inverting)
The enzyme from yeast catalyses the reversible conversion specifically between the alpha-D-glucose 6-phosphate and beta-D-fructofuranose 6-phosphate. The enzyme also catalyses the anomerization of both D-hexose 6-phosphates [7].
CAS REGISTRY NUMBER
COMMENTARY hide
9001-41-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
D-fructose 6-phosphate
D-glucose 6-phosphate
show the reaction diagram
-
-
-
r
D-glucose 6-phosphate
D-fructose 6-phosphate
show the reaction diagram
D-fructose 6-phosphate
D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
r
D-glucose 6-phosphate
D-fructose 6-phosphate
show the reaction diagram
-
-
-
-
r
Fructose 6-phosphate
Glucose 6-phosphate
show the reaction diagram
Glucose 6-phosphate
Fructose 6-phosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
D-fructose 6-phosphate
D-glucose 6-phosphate
show the reaction diagram
-
-
-
r
D-glucose 6-phosphate
D-fructose 6-phosphate
show the reaction diagram
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6-phosphogluconate
-
-
GTP
-
competitive inhibitor, also compromises the autocrine motility factor function of the enzyme. The GTP-binding site partially overlaps with the catalytic site. In addition,GTP stabilizes the structure of PGI against heat- and detergent-induced denaturation. GTP is bound in a syn-conformation with the gamma-phosphate group located near the phosphate-binding loop and the ribose moiety positioned away from the active-site residues
insulin-like growth factor binding protein-3
-
both glycosylated and unglycosylated, binding and inhibition of enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.031 - 0.068
D-fructose 6-phosphate
0.18 - 1.04
D-glucose 6-phosphate
169 - 170
D-fructose 6-phosphate
221 - 267.4
D-glucose 6-phosphate
0.0186 - 0.12
fructose 6-phosphate
0.351 - 0.573
glucose 6-phosphate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.6 - 650
D-fructose 6-phosphate
0.04 - 1000
D-glucose 6-phosphate
3330
fructose 6-phosphate
-
isomerase a
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.7 - 1700
D-glucose 6-phosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.063
GTP
-
pH 7.5, 30°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
620
purified wild-type enzyme
500
-
D-glucose 6-phosphate formation, isomerase c
600
-
D-glucose 6-phosphate formation, isomerase b
870
-
D-glucose 6-phosphate formation, isomerase a
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
8.3
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 10
-
about 50% of maximal activity at pH 7 and at pH 10
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
colon carcinomas show increased PGI expression compared to control cells, overview
Manually annotated by BRENDA team
-
3 enzyme variants are due to a specific intracellular cleavage of the enzyme in the malignant cells
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
peripheral blood mononuclear cell
Manually annotated by BRENDA team
-
synovial fluid
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
malfunction
-
PGI/AMF is correlated with breast cancer and poor prognosis in breast cancer. Inhibition of PGI/AMF expression triggers mesenchymal-to-epithelial transition in aggressive mesenchymal-type breast cancer MD-MB-231 cells
metabolism
-
key enzyme in the AMF signaling pathway, overview
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
G6PI_HUMAN
558
0
63147
Swiss-Prot
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
125000
-
isomerase a, sedimentation equilibrium analysis
132000
-
sedimentation velocity ultracentrifugation
50000
-
x * 50000, SDS-PAGE
56000
-
x * 56000, enzyme variant C, SDS-PAGE
57000
-
x * 57000, enzyme variant B, SDS-PAGE
60000
-
x * 60000, enzyme variant A, SDS-PAGE
63000
-
2 * 63000, sedimentation velocity ultracentrifugation of enzyme dissociated in 6 M guanidine/HCl
6320
-
1 * 6320, A-type subunit, + 1 * 69800, B-type subunit, isoenzyme 3, SDS-PAGE
63200
-
2 * 63200, A-type subunit, isoenzyme 1 and 2, SDS-PAGE
69800
70700
-
2 * 70700, isomerase A, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
dimer
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular modeling and dynamics simulation of GTP binding
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A300P
the mutation may affect the folding efficiency of the enzyme protein, the mutant shows reduced expression level and barely detectable activity
D511N
the mutant shows 0.44% activity compared to the wild type enzyme
E495K
E495Q
the mutant shows 0.39% activity compared to the wild type enzyme
H100L
the mutant shows 0.16% activity compared to the wild type enzyme
H389L
inactive
H389R
the mutation at or near the active site highly affects the catalytic efficiency of the enzyme, the mutant shows barely detectable activity
H396L
the mutant shows 4.2% activity compared to the wild type enzyme
I525T
K362A
inactive
L339P
L487F
the mutation decreases the enzyme tolerance to heat or SDS by mechanisms of decreasing packing efficiency
N154Q
the mutant shows 26% activity compared to the wild type enzyme
N386A
the mutant shows 36% activity compared to the wild type enzyme
Q388A
the mutant shows 5.3% activity compared to the wild type enzyme
R273H
the mutation at or near the active site highly affects the catalytic efficiency of the enzyme, the mutant shows barely detectable activity
R347C
R347H
R472H
the mutation weakens network bonding of the enzyme
R75G
the mutation weakens network bonding of the enzyme
R83W
the mutation increases the water-accessible hydrophobic surface
S185A
the mutant shows 29% activity compared to the wild type enzyme
S278L
T195I
T375R
the mutation decreases the enzyme tolerance to heat or SDS by mechanisms of decreasing packing efficiency
V101M
the mutation decreases the enzyme tolerance to heat or SDS by mechanisms of decreasing packing efficiency
Y274F
the mutant shows 46% activity compared to the wild type enzyme
Y341F
the mutant shows 65% activity compared to the wild type enzyme
A346H
-
mutation identified in a patient suffering from chronic nonspherocytic hemolytic anemia. Loss of 82% of enzyme activity, loss of enzyme capability to dimerize. Mutation results in significant changes in erythrocyte metabolism
Q343R
-
mutant enzymes Thr5 to Ile exhibits marked thermal instability. Mutant Thr224 to Met shows normal substrate affinity in spite of slight decrease in both specific activity and thermostability. Mutant Gln343 to Arg and Asp539 to Asn show impaired substrate affinity
R539N
-
mutant enzymes Thr5 to Ile exhibits marked thermal instability. Mutant Thr224 to Met shows normal substrate affinity in spite of slight decrease in both specific activity and thermostability. Mutant Gln343 to Arg and Asp539 to Asn show impaired substrate affinity
T224M
-
mutant enzymes Thr5 to Ile exhibits marked thermal instability. Mutant Thr224 to Met shows normal substrate affinity in spite of slight decrease in both specific activity and thermostability. Mutant Gln343 to Arg and Asp539 to Asn show impaired substrate affinity
T5I
-
mutant enzymes Thr5 to Ile exhibits marked thermal instability. Mutant Thr224 to Met shows normal substrate affinity in spite of slight decrease in both specific activity and thermostability. Mutant Gln343 to Arg and Asp539 to Asn show impaired substrate affinity
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
54.8
the melting temperature of the mutant is 54.8°C
additional information
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
susceptible to oxidation of sulfhydryl groups yielding multiple electrophoretic forms with catalytic activity
-
2838
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
best storage conditions: as crystalline suspension or precipitate in 0.70 saturated ammonium sulfate containing 50 mM triethanolamine buffer, pH 8.3, 1 mM EDTA, 1 mM dithiothreitol
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
MonoQ column chromatography and SP ion-exchange column chromatography
3 enzyme forms: isomerase a, b, and c
-
enzyme variants A, B and C
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli strain DF2145
expression analysis
-
native enzyme and mutant enzymes T5I, T224M, Q343R, D539N
-
PGI, expression analysis in cells from healthy and colon cancer individuals
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Noltmann, E.A.
Aldose-ketose isomerases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
6
271-354
1972
Apis mellifera, Aspergillus niger, Bos taurus, Canis lupus familiaris, Entamoeba sp., Escherichia coli, Homo sapiens, Klebsiella aerogenes, Mycobacterium tuberculosis, Oryctolagus cuniculus, Pisum sativum, Rattus norvegicus, Saccharomyces cerevisiae, Schistosoma mansoni, Sus scrofa, Trypanosoma sp.
-
Manually annotated by BRENDA team
Tsuboi, K.K.; Fukunaga, K.
Phosphoglucose isomerase from human erythrocyte. Preparation and properties
J. Biol. Chem.
246
7586-7594
1971
Homo sapiens
Manually annotated by BRENDA team
Gracy, R.W.; Tilley, B.E.
Phosphoglucose isomerase of human erythrocytes and cardiac tissue
Methods Enzymol.
41B
392-400
1975
Homo sapiens
Manually annotated by BRENDA team
Sun, A.Q.; Yuksel, K._.; Jacobson, T.M.; Gracy, R.W.
Isolation and characterization of human glucose-6-phosphate isomerase isoforms containing two different size subunits
Arch. Biochem. Biophys.
283
120-129
1990
Homo sapiens
Manually annotated by BRENDA team
Baumann, M.; Brand, K.
Purification and characterization of phosphohexose isomerase from human gastrointestinal carcinoma and its potential relationship to neuroleukin
Cancer Res.
48
7018-7021
1988
Homo sapiens
Manually annotated by BRENDA team
Kanno, H.; Fujii, H.; Miwa, S.
Expression and enzymatic characterization of human glucose phosphate isomerase (GPI) variants accounting for GPI deficiency
Blood Cells Mol. Dis.
24
54-61
1998
Homo sapiens
Manually annotated by BRENDA team
Muraki, Y.; Matsumoto, I.; Chino, Y.; Hayashi, T.; Suzuki, E.; Goto, D.; Ito, S.; Murata, H.; Tsutsumi, A.; Sumida, T.
Glucose-6-phosphate isomerase variants play a key role in the generation of anti-GPI antibodies: possible mechanism of autoantibody production
Biochem. Biophys. Res. Commun.
323
518-522
2004
Homo sapiens
Manually annotated by BRENDA team
Repiso, A.; Oliva, B.; Vives Corrons, J.L.; Carreras, J.; Climent, F.
Glucose phosphate isomerase deficiency: enzymatic and familial characterization of Arg346His mutation
Biochim. Biophys. Acta
1740
467-471
2005
Homo sapiens
Manually annotated by BRENDA team
Mishra, S.; Raz, A.; Murphy, L.J.
Insulin-like growth factor binding protein-3 interacts with autocrine motility factor/phosphoglucose isomerase (AMF/PGI) and inhibits the AMF/PGI function
Cancer Res.
64
2516-2522
2004
Homo sapiens
Manually annotated by BRENDA team
Schaller, M.; Stohl, W.; Benoit, V.; Tan, S.M.; Johansen, L.; Ditzel, H.J.
Patients with inflammatory arthritic diseases harbor elevated serum and synovial fluid levels of free and immune-complexed glucose-6-phosphate isomerase (G6PI)
Biochem. Biophys. Res. Commun.
349
838-845
2006
Homo sapiens
Manually annotated by BRENDA team
Yanagawa, T.; Funasaka, T.; Tsutsumi, S.; Hu, H.; Watanabe, H.; Raz, A.
Regulation of phosphoglucose isomerase/autocrine motility factor activities by the poly(ADP-ribose) polymerase family-14
Cancer Res.
67
8682-8689
2007
Homo sapiens
Manually annotated by BRENDA team
Funasaka, T.; Hu, H.; Hogan, V.A.; Raz, A.
Down-regulation of phosphoglucose isomerase/autocrine motility factor expression sensitizes human fibrosarcoma cells to oxidative stress leading to cellular senescence
J. Biol. Chem.
282
36362-36369
2007
Homo sapiens
Manually annotated by BRENDA team
Dobashi, Y.; Watanabe, H.; Sato, Y.; Hirashima, S.; Yanagawa, T.; Matsubara, H.; Ooi, A.
Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas
J. Pathol.
210
431-440
2006
Homo sapiens
Manually annotated by BRENDA team
Lin, H.; Kao, Y.; Chen, S.; Meng, M.
Effects of inherited mutations on catalytic activity and structural stability of human glucose-6-phosphate isomerase expressed in Escherichia coli
Biochim. Biophys. Acta
1794
315-323
2009
Homo sapiens (P06744), Homo sapiens
Manually annotated by BRENDA team
Funasaka, T.; Hogan, V.; Raz, A.
Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer
Cancer Res.
69
5349-5356
2009
Homo sapiens
Manually annotated by BRENDA team
Tsutsumi, S.; Fukasawa, T.; Yamauchi, H.; Kato, T.; Kigure, W.; Morita, H.; Asao, T.; Kuwano, H.
Phosphoglucose isomerase enhances colorectal cancer metastasis
Int. J. Oncol.
35
1117-1121
2009
Homo sapiens
Manually annotated by BRENDA team
Araki, K.; Shimura, T.; Yajima, T.; Tsutsumi, S.; Suzuki, H.; Okada, K.; Kobayashi, T.; Raz, A.; Kuwano, H.
Phosphoglucose isomerase/autocrine motility factor promotes melanoma cell migration through ERK activation dependent on autocrine production of interleukin-8
J. Biol. Chem.
284
32305-32311
2009
Homo sapiens
Manually annotated by BRENDA team
Somarowthu, S.; Brodkin, H.R.; DAquino, J.A.; Ringe, D.; Ondrechen, M.J.; Beuning, P.J.
A tale of two isomerases: compact versus extended active sites in ketosteroid isomerase and phosphoglucose isomerase
Biochemistry
50
9283-9295
2011
Homo sapiens (P06744), Homo sapiens
Manually annotated by BRENDA team
Lin, H.Y.; Liu, J.H.; Cheng, K.L.; Lin, J.Y.; Liu, N.R.; Meng, M.
A novel binding of GTP stabilizes the structure and modulates the activities of human phosphoglucose isomerase/autocrine motility factor
Biochem. Biophys. Rep.
2
14-22
2015
Homo sapiens
Manually annotated by BRENDA team